| Down-regulation of CIBZ, a novel substrate of caspase-3, induces apoptosis. | |
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MedLine Citation:
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PMID: 18375381 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously identified and characterized a murine BTB domain-containing protein, CIBZ (ZBTB38 in human), that interacts with CtBP and binds to methylated CpGs. However, its physiological function remained unknown. As CtBP is reportedly involved in p53-independent programmed cell death, we examine here whether CIBZ is associated with apoptosis. We found that CIBZ was highly expressed in proliferating C2C12 cells but that its expression levels decreased upon induction of apoptosis by serum starvation. Knockdown of CIBZ by small interfering RNA in C2C12 cells induced apoptosis, as determined by an increase of annexin V/propidium iodide labeling, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase. CIBZ inhibition also activated caspase-7 and caspase-9, suggesting that CIBZ-associated apoptosis occurs through the mitochondrial pathway. Notably, knockdown of CIBZ in p53(-/-) mouse embryonic fibroblast cells also activated caspase-3 and cleavage of poly(ADP-ribose) polymerase, indicating that CIBZ-associated apoptosis is mediated by a p53-independent pathway; however, because both common and distinct targets are regulated by CIBZ- and CtBP-associated apoptosis, we conclude that more than one pathway is involved. Finally, using mutagenesis and an in vitro caspase cleavage assay, we show that CIBZ is a novel substrate of caspase-3 and identify two caspase-3 recognition sites. These findings indicate, collectively, that CIBZ plays an important role by participating in the negative regulation of apoptosis in murine cells. |
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Authors:
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Yu Oikawa; Eishou Matsuda; Tomonori Nishii; Yasumasa Ishida; Masashi Kawaichi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-03-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 283 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-19 Completed Date: 2008-07-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 14242-7 Citation Subset: IM |
Affiliation:
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Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, Nara, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Apoptosis* Caspase 3 / metabolism* Cell Line Down-Regulation* Humans Mice Mice, Knockout RNA, Small Interfering / genetics Repressor Proteins / chemistry, genetics, metabolism* Sequence Alignment Substrate Specificity Tumor Suppressor Protein p53 / deficiency, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/CIBZ protein, mouse; 0/RNA, Small Interfering; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3 |
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